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Variance in disease expression in monogenetic disorders has been attributed to environmental and/ or other genetic factors. This is especially true for inherited predispositions to malignancy where phenotypic expression cannot be adequately explained by a single causative genetic factor. In regard to inherited predispositions to malignancies such as breast cancer or colorectal cancer a growing body of evidence is accumulating that strongly suggests genetic modifiers of disease risk are important players when (or if) mutation carriers develop disease. The search for modifier genes continues as a result of inconsistencies between reports of the effect of the modifier on different cohorts of patients diagnosed with the same disease and the modifying effects of candidate genes being inconsistent in different inherited diseases. The selection of modifier genes has until recently been based on the candidate gene approach which is now to some extent being superseded by genome-wide association studies. Notwithstanding, the candidate gene approach has resulted in some significant insights into the role of genetic modifying factors. The choice of candidate gene to investigate can; however, be problematic and one approach is to investigate genes that have a plausible biological role in either the initiation or progression of disease

Modifier Genes and HNPCC: Variable phenotypic expression in HNPCC and the search for modifier genes